This invention relates to the recovery of substances secreted by cells. More particularly, this invention relates to the recovery of cell products produced by encapsulated cells.
It is known that cells may be grown within capsules having semipermeable membranes. The encapsulated cells are dispersed in a cell growth medium which includes all components necessary for cell metabolism and ongoing viability. The encapsulated cells may be modified cells, such as hybridomas or myelomas, adapted to produce large quantities of cell products such as proteins or other substances of interest. Typically, the capsule membranes are permeable to molecules having a lower molecular weight such as ions, amino acids, cell wastes and cell nutrients suspended in the growth medium. The membranes generally are constructed so as to be impermeable to higher molecular weight materials, particularly products secreted by the cells. Techniques for cell encapsulation are disclosed in U.S. Pat. Nos. 4,409,331 to Lim; 4,251,387 to Lim et al; and 4,352,883 to Lim, each of which is hereby incorporated by reference. It is possible to regulate the permeability of the capsule membrane as disclosed in the above-referenced patents and as disclosed in copending U.S. application Ser. No. 579,494 which is also hereby incorporated by reference.
The membranes typically used to encapsulate viable cells are generally constructed of a first, gellable layer of a polysaccharide material such as an alkalai metal alginate. This first layer is permanently cross linked upon contact with a polymer having plural reactive groups such as polylysine. A more detailed description of the capsule membranes and their formation techniques is provided in the above-referenced patents, particularly U.S. Pat. No. 4,352,883.
Of particular interest in the field of biotechnology is the genetic modification of cells to yield cells capable of secreting relatively large quantities of a product of interest such as proteins or other biological agents having important medical, pharmaceutical, or industrical applications. Current noteworthy products of modified cells include monoclonal antibodies. Although biological agents such as monoclonal antibodies may be sufficiently and conveniently produced by cells and collected within membranes which enclose the cells, as described above, the recovery of the cell product from within the encapsulating membrane can be quite tedious.
Recovery of the cell product from within the volume defined by the capsule membranes typically involves a number of tedious manual steps during which there exists the possibility that the cell product will be contaminated, or that all or part of the product will be lost or damaged to the extent that it is not usable. One important step of the typical recovery process is to rupture the capsule membrane to release the encapsulated cell product. Eventually the cell product must be isolated from the capsule membrane debris and the cells. Other steps such as washing and purification are also involved in this process. As a result of the numerous manual steps involved in this process, the recovery of a relatively pure cell product from within capsules membranes is quite time consuming and economically inefficient.
Accordingly, there is a need for a system or apparatus which automatically and/or sequentially performs the steps necessary to recover the cell product from the encapsulated environment with little or no human intervention. A useful apparatus would decrease the time necessary to recover cell products and would reduce the chance of contamination or loss of the product, thereby making the production and collection of cell products more economically feasible.